Evidence map›Paper›PMID 34669421›Full record

ArticleNano letters2022

Orthogonal Design of Experiments for Optimization of Lipid Nanoparticles for mRNA Engineering of CAR T Cells.

Margaret M Billingsley, Alex G Hamilton, David Mai, Savan K Patel, Kelsey L Swingle, Neil C Sheppard, Carl H June, Michael J Mitchell

Open access · greenAbstract read
In one paragraph

Article in Nano letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
9.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

94 citing papers in PubMed, 161 citations in OpenAlex.

  1. Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026
    Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  7. Review
  8. Review
  9. Article
  10. Cationic mRNA Lipid Nanoparticles for Ex Vivo NanoCAR-T Cell Engineering.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  11. Beyond autologousMolecular therapy. Oncology · 2026
    Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article

34 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Margaret M BillingsleyDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.ORCID 0000-0003-4499-9066
Alex G HamiltonDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
David MaiDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Savan K PatelDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Kelsey L SwingleDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Neil C SheppardAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Carl H JuneAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Michael J MitchellDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.ORCID 0000-0002-3628-2244
University of Pennsylvania · USCalifornia Institute for Regenerative Medicine · US

Funding

TRAINING IN HIV PATHOGENESIST32AI007632 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Frederic D Bushman, James L. Riley · 2000 to 2026
$10.6M
In utero gene editing to cure a metabolic liver diseaseR01DK123049 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI PERANTEAU, WILLIAM H. · 2020 to 2024
$3.7M
Targeting stem-like cells and their niche in pancreatic cancerR37CA244911 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Tuomas Tammela · 2020 to 2026
$3.4M
A data-driven drug delivery (4D) platform for probing and treating the chemoresistant bone marrow microenvironmentDP2TR002776 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, MICHAEL J · 2018 to 2018
$2.4M
Modular approach for the delivery of antibodies into the cytoplasm of cellsR01CA241661 · NCI · UNIVERSITY OF PENNSYLVANIA · PI TSOURKAS, ANDREW · 2019 to 2023
$1.8M
Ionizable lipid nanoparticles for the delivery of mRNA for CAR T cell engineeringF31CA260922 · NCI · UNIVERSITY OF PENNSYLVANIA · PI BILLINGSLEY, MARGARET M. · 2021 to 2022
$77k
NCATS NIH HHS DP2 TR002776NCI NIH HHS F31 CA260922NCI NIH HHS R01 CA241661NCI NIH HHS R37 CA244911NIAID NIH HHS T32 AI007632NIDDK NIH HHS R01 DK123049
6 · The paper itself

Abstract

Viral engineered chimeric antigen receptor (CAR) T cell therapies are potent, targeted cancer immunotherapies, but their permanent CAR expression can lead to severe adverse effects. Nonviral messenger RNA (mRNA) CAR T cells are being explored to overcome these drawbacks, but electroporation, the most common T cell transfection method, is limited by cytotoxicity. As a potentially safer nonviral delivery strategy, here, sequential libraries of ionizable lipid nanoparticle (LNP) formulations with varied excipient compositions were screened in comparison to a standard formulation for improved mRNA delivery to T cells with low cytotoxicity, revealing B10 as the top formulation with a 3-fold increase in mRNA delivery. When compared to electroporation in primary human T cells, B10 LNPs induced comparable CAR expression with reduced cytotoxicity while demonstrating potent cancer cell killing. These results demonstrate the impact of excipient optimization on LNP performance and support B10 LNPs as a potent mRNA delivery platform for T cell engineering.

Indexed as

NanoparticlesHumansLiposomesRNA, MessengerT-LymphocytesLipid NanoparticlesLiposomesRNA, MessengerCAR Tlipid nanoparticlesmRNA deliveryT cell engineering

Identifiers

PMID34669421
PMCPMC9335860
OpenAlexW3207676521

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.